Borna disease virus: new aspects on infection, disease, diagnosis and epidemiology

A 'disease of the head' affecting horses, as described in the 17th Century is now known as Borna disease. Research over the past 100 years has established that the aetiological agent, Borna disease virus (BDV), is an unsegmented, single- and negative-stranded, enveloped ribonucleic acid (RNA) virus which represents the family Bornaviridae in the order Mononegavirales. The virus exists world-wide in horses, sheep, cattle, cats, dogs and ostriches. The infection can be fatal, but the majority of carriers are persistently infected without showing symptoms. The association with psychiatric diseases in humans led to an international explosion of research on BDV, with centres established in Germany, the United States of America and Japan. Experimental infections of tree shrews and rats served to examine the effects of persistent and overt disease, most excitingly, virus-induced behavioural changes, and emotional and learning deficits. This 'emerging' virus infection shows complex pathogenetic mechanisms in the nervous system, but also spreads through myelo-monocytic cells. Diagnosis can be made serologically, but detection of antigen markers in peripheral white blood cells, combined with nucleic acid amplification is more profitable. Comparative RNA studies reveal an unusually high genetic homology of viruses. Isolates recovered from humans and equines suggest species-specificity. Vaccination is not an advisable strategy, but antiviral therapy, especially with amantadine sulphate, promises efficacy in human mood disorders, and is effective in vitro. Infections with BDV follow a vulnerability principle to cause disease. Although cross-species transmission of this commensal virus has not been proven, zoonotic aspects of BDV should be carefully considered.     

Borna disease.

Borna disease virus, a newly classified nonsegmented negative-strand RNA virus with international distribution, infects a broad range of warm-blooded animals from birds to primates. Infection causes movement and behavioral disturbances reminiscent of some neuropsychiatric syndromes. The virus has not been clearly linked to any human disease; however, an association between infection with the virus and selected neuropsychiatric disorders has been suggested. We reviewed recent advances in Borna disease virus research, focusing on evidence of infection in humans.     

Shrews as reservoir hosts of borna disease virus

Borna disease virus (BDV) is the causative agent of severe T-cell-mediated meningoencephalitis in horses, sheep, and other animal species in central Europe. Here we report the first unequivocal detection of a BDV reservoir species, the bicolored white-toothed shrew, Crocidura leucodon, in an area in Switzerland with endemic Borna disease.     

博尔纳病病毒感染与神经胶质瘤相关性研究

目的探讨博尔纳病病毒(BDV)感染与神经胶质瘤发生的可能相关性。方法用Western-blot方法,对23例神经胶质瘤患者和23例脑外伤患者血清中BDV-p24/p40特异性抗体进行检测。结果 23例神经胶质瘤患者血清中BDV-p24/p40抗体阳性4例,阳性率为17.4%;脑外伤患者血清标本中无BDV-p40抗体检出,阳性率为0%。结论神经胶质瘤患者血清中存在博尔纳病病毒的感染。     

Wild birds as a possible natural reservoir of Borna disease virus

The natural reservoir of Borna disease virus (BDV) is unknown. In this paper, we show that mallards (Anas platyrhyncos) and jackdaws (Corvus monedula) can be subclinically infected carriers of this virus. From faecal samples collected at a bird pond, we were able to amplify fragments of the BDV p24 and p40 genes. Following cloning and sequencing, a phylogenetic analysis revealed that these birds carry strains of BDV closely related to but distinct from the reference strains BDV V and He/80. To our knowledge, this is the first confirmed finding of BDV in wild birds.     

博尔纳病病毒感染与病毒性脑炎发病的关系

目的 检测宁夏地区不明原因病毒性脑炎患者外周血单个核细胞(PBMCs)博尔纳病病毒(BDV)携带情况,分析BDV与标准病毒株之间的同源性.探讨BDV感染性疾病与不明原因病毒性脑炎之间的关系,同时也为部分病毒性脑炎的病因学诊断及其防治提供实验依据.方法 采用荧光定量巢式反转录酶聚合酶链反应(FQ-nRT-PCR)检测宁夏地区不明原因病毒性脑炎患者及正常人PBMCs BDV p24基因片段,并对其中阳性扩增产物进行基因序列测定,然后采用BLAST软件以及DNAsist 5.0软件对测序结果进行分析.结果 病毒性脑炎组样本BDVp24基因片段FQ-nRT-PCR阳性率(10.17%)显著高于正常对照组(0%)(P＜0.05).病毒性脑炎患者检出BDVp24基因片段的核苷酸序列与马BDV标准病毒株H3915序列同源性为97.67%,与H1766株比较在3个位点出现一致性突变(nt1659 T→C,nt1668 A→G,nt1674 T→C;突变率为3.49%);与strain V株比较在4个位点出现一致性突变(nt1648 C→T,nt1658 G→A,nt1667 A→G,nt1673 T→C;突变率为4.65%),但编码的氨基酸相同.证实扩增所得目的 基因片段确系BDV p24的相应片段.结论 宁夏地区不明原因病毒性脑炎患者中存在BDV感染,提示部分不明原因病毒性脑炎的发生可能与BDV感染有关.且该BDVp24扩增产物核苷酸序列与标准病毒株高度同源性,与马源strain H3915同源性最高.     

新疆伊犁地区不同品种犬博尔纳病病毒自然感染调查

目的 调查新疆伊犁地区不同品种犬博尔纳病病毒(BDV)流行现状和分析其可能的种系来源.方法 采用改进的巢式反转录PCR(nRT-PCR)方法,检测犬外周血单核细胞(PBMCs)BDV磷蛋白(p24)RNA基因片段.用BDV核蛋白(p40)RNA片段和质粒PMD19标准品验证p24阳性产物,排除可能的假阳性.验证后的阳性产物进行基因测序、同源比对、氨基酸序列和系统发生学分析.结果 8个品种150只犬中,仅哈萨克牧羊犬检出BDV p24片段,阳性率为11.0%(10/91).基因序列与德国马He/80和德国绵羊S6病毒株同源相似度分别为99.2%和95.7%,氨基酸相似度为100%和89.3%,亲缘关系与He/80最近,其次为S6.结论 新疆伊犁地区哈萨克牧羊犬可能存在BDV自然感染,其流行株与该地区伊犁马感染的He/80和引进德国美利奴绵羊的S6病毒株有关.     

遵义市及周边地区博尔纳病毒感染分子流行病学研究

目的 探讨博尔纳病毒(BDV)在遵义市及周边地区流行状况.方法 采用荧光定量巢式反转录酶聚合酶链反应(FQ-nRT-PCR)检测43例病毒性脑炎(VE)患者、9例多发性硬化(MS)患者、7例急性吉兰-巴雷综合征(GBS)患者、5例帕金森病(PD)患者、98名健康人外周血液单个核细胞(PBMC)、300只山羊PBMC中BDV p24基因片段.对阳性产物进行基因序列测定,氨基酸顺序及同源性分析,并分析BDV分子流行病学特点.结果 BDV p24基肉片段阳性率VE患者为13.95%,MS患者为22.22%,而GBS和PD患者及健康人中未检出.VE和MS患者检出率明显高于健康人(0%,P<0.05),山羊BDV p24基冈片段阳性率为0.67%,与健康人对比差异尢统计学意义(P>0.05);VE和MS患者测序结果 相同与GenBank提供的strain V毒株比较同源性为96.51%,有3个位点出现一致性沉寂突变,BDV/MDCK毒株比较同源性为97.67%,有2个位点出现一致性沉寂突变,与C6BV毒株比较有2个位点出现一致性沉寂突变,其山羊中BDV p24基因片段测序结果 与GenBank提供的strain V毒株比较同源性为96.51%,有3个位点出现一致性沉寂突变,与BDV/MDCK毒株比较同源性为96.51%,有3个位点出现一致性沉寂突变,与C6BV毒株比较同源性为96.51%,有3个位点出现一致性沉寂突变,但所编码的氨基酸没有改变.结论 遵义市及周边部分地区VE、MS可能与BDV感染有关,人类感染BDV可能存在动物源性.     

新疆伊犁地区不同品种犬博尔纳病病毒自然感染调查

目的 调查新疆伊犁地区不同品种犬博尔纳病病毒(BDV)流行现状和分析其可能的种系来源.方法 采用改进的巢式反转录PCR(nRT-PCR)方法,检测犬外周血单核细胞(PBMCs)BDV磷蛋白(p24)RNA基因片段.用BDV核蛋白(p40)RNA片段和质粒PMD19标准品验证p24阳性产物,排除可能的假阳性.验证后的阳性产物进行基因测序、同源比对、氨基酸序列和系统发生学分析.结果 8个品种150只犬中,仅哈萨克牧羊犬检出BDV p24片段,阳性率为11.0%(10/91).基因序列与德国马He/80和德国绵羊S6病毒株同源相似度分别为99.2%和95.7%,氨基酸相似度为100%和89.3%,亲缘关系与He/80最近,其次为S6.结论 新疆伊犁地区哈萨克牧羊犬可能存在BDV自然感染,其流行株与该地区伊犁马感染的He/80和引进德国美利奴绵羊的S6病毒株有关.     

新疆伊犁地区马群中博尔纳病病毒自然感染调查

目的 了解新疆伊犁地区马群中博尔纳病病毒(BDV)的流行状况,分析该病毒的种系来源.方法 采用改进的巢式反转录PCR(nRT-PCR)方法对新疆伊犁地区120匹马的外周血单个核细胞(PBMC)及脑组织中的BDV p24基因片段进行检测,对阳性产物进行基因序列测定和同源性分析.结果 有3匹马外周血和腩组织中同时检测到BDV,阳性率为2.5%(3/120).扩增产物序列与其他国外马源BDV分离株同源性>93%,与标准株He/80同源性达到98%以上.结论 新疆伊犁地区马群中存在BDV的自然感染.该地区BDV流行株与标准株He/80存在高度的同源性.     

Borna disease virus: the generation and review of a scientific study

The paper uses interviews and observational data gathered among a group of UK scientists and civil servants responsible for managing a study examining the possible transmission to humans of Borna disease virus (BDV), a disease primarily of farm animals. From a science and technology studies perspective, the paper examines the social processes whereby this scientific problem (possible human transmission) was constituted as a worthy topic of scientific investigation, came to receive funding, and was subjected to independent review. It appears that BDV research displays only some of the characteristics of 'post-normal science' with little participation by extended peer communities. Civil servants and scientists reported social interests that were complex and both fractionated and cross-occupational. An important motivation for engaging in the research was the need to maintain investment in pre-existing scientific resources (assay development, virus stocks and an existing epidemiological cohort). In respect of translation theory, influence was a two-way street, with civil servants eager to enrol scientists and represent the interests of science, and with scientists presenting themselves as defenders of the public good. Despite the dynamic character of scientific debate, the 'career' of BDV investigation appears to have ended in disengagement, rather than closure.     

宁夏地区人畜BDV p24基因系统发生树构建和序列分析

目的 了解宁夏及其周边地区博尔纳病病毒(BDV)的感染状况和基因特征及其种系发生来源.方法 采用巢式反转录实时荧光定量聚合酶链反应(FQ-nRT-PCR),检测119例病毒性脑炎(VE)患者和其密切接触的患病或健康牛205头、绵羊978只及脑血管病患者46例、多发硬化患者13例的外周血单核细胞BDVp24片段,检出的阳性序列连同前期检出的宁夏绵羊、VE患者和抑郁症患者阳性BDVp24基因序列与GenBank中5个国家7个动物种属29例BDVp24基因序列进行比对,分析其核苷酸和氨基酸序列的同源性,重新构建基因系统发生树.结果 23例阳性检测标本连同3例前期检测序列基因聚合分析显示核苷酸之间的同源相似度为96.5%～100.0%,氨基酸的同源相似度为95.3%～100.0%.与德国马源性标准株HE80同源相似度较高.构建基因的系统发生树发现宁夏绵羊、VE患者和抑郁症患者同德国马和绵羊、奥地利马都各自形成了独立的支系,其余样本形成混合支系,其中宁夏的VE患者、牛、绵羊同德围马、日本绵羊形成德国-中国宁夏-日本混合支系.结论 宁夏及其周边地区人和动物BDV的感染,存在区域源性BDV独立株和国外传人基冈保守株的多源状态.     

Targeting Marek's disease virus by RNA interference delivered from a herpesvirus vaccine

Live attenuated herpesvirus vaccines such as herpesvirus of turkey (HVT) have been used since 1970 for the control of Marek's disease (MD), a highly infectious lymphoproliferative disease of poultry. Despite the success of these vaccines in reducing losses from the disease, Marek's disease virus (MDV) strains have shown a continuing increase in virulence, presumably due to the inability of the current vaccines in preventing MDV replication. The highly specific and effective nature of RNA interference (RNAi) makes this technology particularly attractive for new antiviral strategies. In order to exploit the power of RNAi-mediated suppression of MDV replication in vivo delivered through existing vaccines, we engineered recombinant HVT expressing short hairpin RNA (shRNA) against MDV genes gB and UL29. The levels of protection induced by the RNAi-expressing HVT against virulent virus challenge were similar to the parent pHVT3 virus. However, chickens vaccinated with recombinant HVT expressing shRNA showed moderate reduction of challenge virus replication in blood and feather samples. Delivery of RNAi-based gene silencing through live attenuated vaccines for reducing replication of pathogenic viruses is a novel approach for the control of infectious diseases.     

寨卡病毒病流行病学概述

寨卡病毒病是一种由寨卡病毒引起的,主要通过伊蚊传播的新发急性病毒性传染病,尚无疫苗和特异性治疗药物。为了加强对寨卡病毒病流行病学特征的了解,本文通过Medline数据库检索寨卡病毒病相关信息,结合相关政府部门、国际卫生组织报告等资料对寨卡病毒病流行病学特征进行综述。目前,该病主要在美洲地区流行,呈快速蔓延之势,34个国家存在病毒本地传播,多个国家报告输入病例。该病临床表现通常较轻,死亡罕见,部分病例可出现神经系统综合征,婴儿出生缺陷等较严重的后果,引起国际社会广泛关注,中国存在因输入病例引发的疫情局部扩散的风险。但该病是一种可防可控的传染病,只要各项策略和措施落实到位,就能够有效控制疫情扩散。     

Vaccination against the feline leukaemia virus: outcome and response categories and long-term follow-up

Feline leukaemia virus (FeLV) is a pathogen inducing fatal disease in cats worldwide. By applying sensitive molecular assays, efficacious commonly used FeLV vaccines that protect cats from antigenaemia were found not to prevent proviral integration and minimal viral replication after challenge. Nonetheless, vaccines protected cats from FeLV-associated disease and prolonged life expectancy. The spectrum of host response categories was refined by investigating plasma viral RNA loads. All cats initially fought similar virus loads, although subsequently loads were associated with infection outcomes. Persistence of plasma viral RNA was moderately associated with reactivation of FeLV infection. In conclusion, sensitive molecular assays are important tools for reviewing pathogenesis of FeLV infection.     

Viral and host determinants of RNA virus vector replication and expression

Positive-strand RNA viruses have proven to be valuable vectors for delivery and expression of antigens for direct vaccination of animals and vaccine production in plants. However, optimal use of these viruses as vectors for vaccine and other purposes is limited by incomplete understanding of their replication pathways and associated constraints on inserted foreign genes. Further insights into RNA virus vector design and optimization are emerging from recent advances on the function of viral RNA replication factors, the nature of the viral RNA replication complex as a membrane-bounded compartment sequestering replication components from competing processes and host defenses, and identification of surprisingly diverse host genes contributing to many virus replication steps.     

Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage–Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.     

Hepatitis E virus and neurologic disorders

Information about the spectrum of disease caused by hepatitis E virus (HEV) genotype 3 is emerging. During 2004-2009, at 2 hospitals in the United Kingdom and France, among 126 patients with locally acquired acute and chronic HEV genotype 3 infection, neurologic complications developed in 7 (5.5%): inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Three cases occurred in nonimmunocompromised patients with acute HEV infection, and 4 were in immunocompromised patients with chronic HEV infection. HEV RNA was detected in cerebrospinal fluid of all 4 patients with chronic HEV infection but not in that of 2 patients with acute HEV infection. Neurologic outcomes were complete resolution (n = 3), improvement with residual neurologic deficit (n = 3), and no improvement (n = 1). Neurologic disorders are an emerging extrahepatic manifestation of HEV infection.